The objective is to investigate the ionic processes underlying cardiac excitation and contraction. The investigation focusses on the role of the intracellular concentrations of K and Na and on cross-ionic interactions. The chosen preparation, frog ventricular muscle has been extensively investigated and the contractile process is well controlled by the clampable surface membrane due to a virtual lack of sarcoplasmic reticulum. The single sucrose gap voltage-clamp technique is used to control the membrane potential and to measure the membrane current and the isometric tension. The intracellular concentration of K is monitored simultaneously by measuring the radioactive emission from the preparation when 42K is added to the perfusate. Interventions known to decrease the intracellular K concentration (low temperatures, low extracellular K concentrations, long depolarizing clamp pulses, rapid stimulation and strophantidin) will be used to alter the intracellular ionic composition. The investigation will attempt to answer the questions: Passive membrane currents: a) How are the membrane currents influenced by the intracellular ion concentrations? b) Is the conductance of the resting membrane decreased when the intracellular K concentration is decreased? c) Is the threshold of excitation decreased under these conditions? d) Is the speed of propagation decreased? Active transport: e) Is the Na-K exchange pump electrogenic? f) What is the coupling ratio for Na and K? g) Does the activity of the pump alter the shape of the action potential? Excitation-contraction coupling: h) How do the intracellular concentrations of K and Na influence the tension-voltage relations? i) To what extent is contraction controlled by a Na-Ca exchange mechanism?